A study of tucatinib vs. placebo in combination with ado-trastuzumab emtansine (T-DM1) for subjects with advanced or metastatic HER2+ breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seagen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Nov 2020 → ongoing

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Seagen Inc

External identifiers

EU CT number

2024-514733-38-00

EudraCT number

2019-005017-39

ClinicalTrials.gov

NCT03975647

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Therapy, Safety, Pharmacodynamic

Compare progression-free survival (PFS) by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 between treatment arms

Secondary objectives 4

1. Compare overall survival (OS) between treatment arms
2. Compare PFS by investigator assessment per RECIST v1.1 in subjects with brain metastases at baseline (PFS.BM per investigator) between treatment arms
3. Compare the objective response rate (ORR) by investigator assessment per RECIST v1.1 between treatment arms
4. Compare overall survival in subjects with brain metastases at baseline (OS.BM) between treatment arms

Conditions and MedDRA coding

Unresectable locally-advanced or metastatic HER2+ breast cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory
2. History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination
3. Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy
4. Measurable or non-measurable disease assessable by RECIST v1.1
5. ECOG performance status score of 0 or 1
6. CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must have at least one of the following: (a) No evidence of brain metastases (b) Untreated brain metastases not needing immediate local therapy (c) Previously treated brain metastases 1. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy 2. Participants treated with CNS local therapy for newly identified lesions or previously treated and progressing lesions may be eligible to enroll if all of the following criteria are met: (i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 14 days prior to first dose, or time since surgical resection is at least 28 days. (ii) Other sites of evaluable disease are present 3. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

Exclusion criteria 2

1. Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity).
2. CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must not have any of the following: 1. Any untreated brain lesions >2 cm in size 2. Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent). 3. Any brain lesion thought to require immediate local therapy 4. Known or concurrent leptomeningeal disease as documented by the investigator 5. Poorly controlled generalized or complex partial seizures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS per RECIST v1.1, as determined by investigator assessment

Secondary endpoints 4

1. OS
2. PFS.BM per RECIST v1.1, as determined by investigator assessment
3. ORR per RECIST v1.1, by investigator assessment
4. OS.BM

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seagen Inc.

Sponsor organisation

Seagen Inc.

Address

21823 30th Drive Southeast

City

Bothell

Postcode

98021-3907

Country

United States

Scientific contact point

Organisation

Seagen Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Seagen Inc.

Contact name

Clinical Medical Lead

Third parties 9

Locations

8 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications